Irradiated substance and compound and method of preparing the same

ABSTRACT

BACTERICIDE AND A CELL AND TISSUE HEALER, NON-IRRITATING TO THE USER.   THIS DISCCLOSURE DEALS WITH NOVEL IRRADIATED SUBSTANCES AND COMPOUNDS PREFERABLY CONTAINING A RATHER CRITICAL CONCENTRATION OF COLLOIDAL PARTICULATE HEAVY METALS INCLUDING THE NOBLE HEAVY AND TRANSITION METALS, AND HAVING AMONG OTHER ADVANTAGEOUS USES, UNUSUAL EFFICACY AS A

June 25, 1974 J. L oRlNA ETAL 3,819,820 IRRADIATED SUBSTANCE AND COIPOUND' AND METHOD 0F PREPARING THE SAME Filed Sept. 18. 1969 SPEED or: REACHON 0N sTAPHuococcus AUREus (No. oF coLomEs DE sTRoYeo PER MIN 5 RATE E F H CACI IOW-'AG AS STND. Il, f /f Alg ma INVENTORS JOHN LoRmA f f Gr. RoNALv ALulsY ,f NORMAN D.\ ouo l* k f l ROBERT H. RmEs coNcENTTwN (PERCENT) ATTORNEYS 3,819,820 IRRADIATED SUBSTANCE AND COMPOUND AND METHOD OF PREPARING THE SAME John Lorina, 30 Pond St., Hull, Mass. 02045; G. Ronald Aluisy, 699 Bridge St., North Weymouth, Mass. 02169; Norman D. Loud, 39 Academy Ave., East Weymouth, Mass. 02169; and Robert H. Rines, 25 Shady Brook Lane, Belmont, Mass. 02178 Continuation-impart of abandoned application Ser. No. 749,141, July 3l, 1968. This application Sept. 18, 1969, Ser. No. 859,141

Int. Cl. A61k 27/04 U.S. Cl. 424--1 14 Claims ABSTRACT OF THE DISCLOSURE This disclosure deals with novel irradiated substances and compounds preferably containing a rather critical concentration of colloidal particulate heavy metals including the noble heavy and transition metals, and having among other advantageous uses, unusual efficacy as a bactericide and a cell and tissue healer, non-irritating to the user.

The present invention relates to radioactivated substances and compounds and methods of preparing the same, being more particularly directed to bacteriaand virus-killing and irritation-healing compounds; the term radioactivated being used to mean irradiation or electrically exciting or charging by ultraviolet, gamma rays, X-rays, beta particles, neutrons, protons, deuterons and the like, all having quantum energy at least as high as ultraviolet, but not long wavelength electromagnetic waves, and with the irradiated substances and compounds of the invention, however, having no detectable residual radioactivity. This application is a continuation-in-part of U.S. application Ser. No. 749,141, filed July 3l, 1968, now abandoned.

While the art is replete with bactericides and diseasecuring compounds of a wide variety of types, they all have limitations and disadvantages that restrict their safe or eicacious usage. As an illustration, m-cresol bactericide, widely used in hospitals and the like for clean rooms and to prevent contamination, requires a sufficiently strong concentration to b'e effective that it becomes irritating to the skin. Rather large doses of X-ray and other radiation have also been employed for bacteria and virus killing and cancer and other disease-treatment or -curing purposes; but again such treatment is attendant upon disadvantages, including high radiation damage.

As explained in said application, underlying the present invention, in summary, is the discovery that, in preferred form, a small critical concentration of irradiated colloidal particulate heavy metals, appropriately combined in a suitable carrier, can accomplish remarkable bactericidal, irritation-dissipating and similar curative functions in such low concentrations as to itself be nonirritating, and, unlike X-rays, free of radioactivity and otherwise harmless of tissue and the like.

An object of the invention, accordingly, is to provide a new and improved irradiated substance and/or compound and method or process of preparing and using the same that shall attain the above and other advantages.

Other objects are to provide novel noble heavy and transition metal chelates of bactericidal and medicinal efficacy.

A further object is to provide novel substances and/r compounds of more general utility, as well.

Other and further objects will be hereinafter set forth and are more particularly delineated in the appended claims.

The invention will now be described with reference to United States Patent() fil the accompanying drawing, FIG. l of which is an experimentally obtained graph illustrating the critical concentration discovery underlying the preferred form of the invention; and

FIG. 2 is a similar graph showing the relative kill efcacy upon Staphylococcus aureus, Escherichia coli and b. subtilis of a number of heavy and transition metals exhibiting the phenomenon underlying such discovery.

That discovery includes the finding that very small critical concentrations of colloidal particulate heavy and transition metals, such as the noble metals of Ag, Au, Pt, Pd, Rh, Ru and Cu, Cd, Re, Ti, Zr, Mo, Mn, Os, Ir, Tb, Pr, Ce, Th, Pa, U, Hf, W, V, Zn, Hg (and to rather minor extents Fe and Co)-all hereinafter generically referred to as the heavy and transition metals-when appropriately radioactivated or irradiated as above-described, can produce the novel results before summarized; while lesser 0r greater concentrations do not function to achieve such results. As before stated, ultraviolet, and electric field generators of, for example, gamma and X-rays, have been found to be effective radioactivators or irradiators for the purposes of the invention; while heat and electromagnetic radiation of longer wavelength than ultraviolet rays were not found to be effective.

As a trst example, a colloidal silver suspension in a non-reactive water carrier solution, in which the particulate silver concentration is limited rather critically to the order of about 1.5 103 grams per cubic centimeter (or about 0.15% by weight) and the silver is irradiated as by a source of gamma radiation, has been found to provide remarkable bactericidal properties despite the minuscule quantity of the silver.

yReferring to FIG. 1, the speed of reaction on Staphylococcus aureus bacteria is plotted along the ordinate in units of colonies destroyed per minute, as a function of concentration of the silver ion, plotted in units of 10*3 grams per cubic centimeter along the abscissa. From this experimentally obtained data, it is evident that the beforementioned concentration of the order of about 1.5)(10*a grams per cubic centimeter is a rather critical and highly unexpected optimum concentration; lower concentrations, such as one-third the same, being rather inetcacious, as are higher concentrations, such as twice as much or greater. This critical concentration-destruction ecacy, moreover, was found to coincide, also, with what might be termed the measured optimum ionization constant (which involves the amount of freely conductive silver ions and the maximum chemical activity or optimum conductivity in a distilled water solution).

Using the standard Frost Little Plate method, a 50% kill ofStaphylococcus aureus was obtained with the above solution in about 4 minutes; and a 95% kill in about 6 minutes.

As still another illustration with a different bacterium, said solution produced a 50% kill of Staphylococcus albus in 7 minutes; and a 95 kill in about 9 minutes.

It is to be observed, moreover, that this minuscule colloidal particulate irradiated silver concentration -is entirely harmless and non-irritating to the skin and free of radioactivity; and yet is comparable in its bactericidal properties to, for example, the widely used m-cresol, which, to the contrary, must be used in such strong concentration to be effective, that it is `decidedly irritating to the user, and, indeed, precautions must be taken to prevent prolonged skin contact with the same.

It has further been found that the irradiation source, if of gamma rays or the like, need not exceed substantially 1.3 microcun'es to produce the desired ecacious product.

As another example, a silver chelate, formed with the alkaloids of the strychnine family (strychnine, brucine and reserpine) in a non-toxic, non-reactive carrier has Staphylococcus Staphylococcus aureus albus 50% kill... 3.5 'minute 6.2 minutes. 95% kill 5.5 minutes 8.4 minutes.

As still a further illustration, with the said chelate coml kill of Staphylococcus albus in the same period, with bined about 140 parts per million in an inert, non-reactive v cornstarch-Water emulsion, similar bactericidal effects have been observed. In this chelate compound, the minute trace proportions of the strychnine and brucine alkaloids were about equal and about twice that of the reserpine alkaloid. In addition, the effective clearing up of acne and psoriasis has also been observed with this compound. Further, skin irritations (effected by needle stroking without leaving time for healing) that have been observed nor- `mally to developu skin cancer tumors sarcoma) on guinea pigs, when periodically covered by this compound (and despite continued needle stroking), progressively healed sufficiently that all indicia of the sarcoma disappeared. Other consistent healing effects have also been observed.

Additional non-toxic systemic and topical carriers, nonreactive with the said critical concentration of radio-activated colloidal heavy metal being used (i.e. the silver, copper, gold or rhenium or other similar heavy or transition-type metal before listed, for example), have also been thus successfully employed, including SDA 401 ethanol, denatured with brucine; inert mineral oil; and a boraxemulsified water solution.

An experimentally determined comparison between the particulated silver obtained from the silver chelate water solution (ultraviolet-irradiated and in the approximately l.5 l03 grams per cubic centimeter concentration) and a `6% solution of presently widely used hexachlorophene, showed the marked bactericidal superiority of the invention for several gram negative and positive bacteria, as follows:

' 100% kill in Vaboutl ten minutes. This is as compared with only relatively slight kills for the same silver colloidal particles, non-irradiated-which, though of some use in certain applications, is not nearly as efficacious as the irradiated particles.

Similarly, each of, for example, irradiated copper, gold, platinum, iridium, manganese, and rhenium,` colloidal particles of the same size range, have been proven effective as bactericides, producing kills of the same bacteria above-listed. Theoretically this would appear to apply to all heavy and transition-type metals, so prepared, though the efficacy will vary with the element. Substantially the same approximately 1.5 10-3 grams per cubic centimeter low-concentration optimum constant of the silver particles, for example, was found to exist for gold, rhenium and copper colloidal particles, with gold being much more efiicacious in time of kill, as indicated in FIG. 2. In the tests shown in FIG. l2, moreover, rhenium proved more efficacious than silver, and copper showed a remarkable efficacy for greater concentrations beyond the low-concentration optimum. Other tested irradiated metals that also show this same substantially 1.5 1(l3 grams/cc. constant include the before-listed Ti, Zr, Mo, Mn, Ru, Rh, Pd, Os, Ir, Pt, Tb, Pr, Ce, Th, Pa, U, Hf, W, V, Zn, Cd and Hg.

Other ultraviolet-irradiated inorganic chelate compounds (including sunlight-irradiated) with particulated heavy and transition metal ions found to be bactericidal in water solution of the above-mentioned concentration are alkaloidal solutions (containing brucine, strychnine and colchicine alkaloids) having trace metals of copper and thallium. These proved to be effective against each of Escherichia coil, Staphylococcus aureus and Bacillus subtils.

Among the healing effects, before-mentioned, is the unbelievably rapid reduction in burn histamine-type pain response, erythema and redness and absence of blister, all effected with both oil and water suspensions of each, for example, of the silver, gold, copper and, to a lesser extent, rhenium colloidal particulated compounds before tested as bactericides.

While it is sufficient to describe an invention in terms of the elements, compounds and results, it sometimes aids in understanding to theorize as the possible operation; though it is distinctly to be understood that the present invention is not dependent upon theories, whether accurate or inaccurate-it being sufficient to describe the invention as it has been found to work in practice and such The finely divided colloidal particles in the substances and compounds of the invention have been found to have a large number (in fact, in some measurements, or more, or an average number) of separate particles of size range between substantially 10-5 and 10-s cm., which are believed to be important to the cell penetration or other effects herein involved. Similarly dimensioned silver particles alone, not derived from chelates, but irradiated with X-rays (gamma), as before described, have also been found to produce substantial bactericidal and healing effects; to wit, such irradiated colloidal silver in water solution in the above-mentioned concentration produced-a that it may be practiced to produce the claimed results.

lIt appears likely, however, that the apparently universal nature of the bactericidal substances of the invention (no bacterium yet tried has not been rapidly killed) may reside in the supplying of appropriately small, unclustered and free heavy metal ions (probably freed by the irridiation or otherwise similarly electrically charged to prevent clustering) that, by induced electron exchange, effect a change (probably a reduction), either catalytically or by chemical combination, in the intracellular oxygen and peroxides generated at or in the vicinity of the cell. In the case of pathogenic organisms, this appears to debili- 93 of Staphylococcus aureus in five minutes, and a 91% 75 tate and destroy the same.

Evidence of further universality has been obtained in the efficacy of, for example, the silver compounds of the invention, against virus such as cow-pox and cold virus.

Concurrently, in the case of animal and human cells, this phenomenon also appears to control the metabolic rate through the oxygen and peroxide control or antioxidant activity or the like, possibly replacing such metal ions at the cells that may have been chemically combined or consumed by disease, radiation or other damage (or, in the case of prevention, that may subsequently be consumed, combined or rendered ineffective). It is an observable fact, however, that a type of healing and unusually rapid outward growth of light pink tissue occurs, void of the usual scabbing and inward slow-healing provided by nature, in diseased, cut and damaged tissue treated with substances of the invention, whether externally or systemically applied, act within the enzymic system to improve cellular efiiciency and healing. Differentiation in action upon strong and weak or diseased cells has been observed in the before-mentioned preliminary cancer studies; it being plausible that either replacement of unsubstituted carbon in benzene ring chains that are carcinogenic in the absence of such substitution, by the readily active freed or free-radical heavy metal ions in the compounds of the invention, or reconstituting of the metabolic oxygencontrol or similar process (or both), is an explanation for the observed phenomena. (See, for example, Chemical Basis of Carcinogenic Activity, G. M. Badger, 1962, p. 23.)

Apart from the noble metals, an interesting observation appears to be, moreover, that the transition metals abovelisted can have a coordination or valence number 4, capable of electron transitions or resonances between the second and third electron orbits. This may account for the apparently universal 1.5 X3 constant previously discussed--the bacteria, all being of substantially the same range of dimensions, perhaps being electromechanically destroyed by such oscillations.

These compounds of the present invention, moreover, have been preliminarily found to assist rather startingly in the slowing or inhibiting of certain processes associated with ageing; specifically, the continual application on a daily basis of an oil dispersion of particulated irradiated silver in the said optimum concentration, as before discussed, has been found to prevent cornification of the skin in cases of ichthyosis wherein a rapid localized ageing takes place as a result of the rapid cellular death rate involved in cornification of the skin.

Another element generally associated with the ageing process is the development of wrinkles accompanying the breakdown of the connective tissue layers of the skin, with resulting loss of elasticity. Such breakdown has been observed to become halted through similar application of the said compounds of the invention.

And still another example of a further element associated with the ageing process that has been found to become obviated through the application of the first-named water solution of the irradiated particulated silver (in the said optimum concentration), is non-infective seborrhea of the scalp involving an acceleration of cellular death rate. The use of such water solution has been found to result in the marked decrease in the index of cebrial activity.

While, moreover, the optimum concentration effect shown in the drawing is obviously highly desirable from' coniderations of economy and possible toxicity, it does prevent continued efficacy upon substantial dilution of the solution. For such purposes and others, accordingly, the solutions may be substantially more concentrated or saturated, as shown to the far right in FIG. 2. (and beyond), though the bactericidal and healing effects do not, except in the case of the particular copper tests indicated, appear to exceed those attainable with the minimal optimum concentration (and in many cases, do not reach the same peak of performance). To permit such dilution to the order of lm), without dropping the efficacy more than about 12%,

a practical use concentration may be centered about 8.3% (by weight) with about 10-15% seemingly a useful commercial or economic (diminishing marginal return) limit.

In the case of irradiated chelates, there lappear to be instances where the metal does not sufficiently dissociate therefrom to control the above effects as the colloidal particulated free metal, and where efficacy increases with concentration on a substantially continual basis. Chelates of coordination number 1 seem to fall within this category. For example, chelates of mercurous, cuprous, silver and aurous compounds have shown highly increased bactericidal kill effects (against Staphylococcus alureus, E. coli and B. subtilis) with about a 4% concentration. Included in these irradiated chelates (which do not appear to produce these results in the absence of irradiation) are tetramine copper-2, bis-ethylene diamine gold-Z, hexacyanomanganate and hexachloro rheniate, all of which have excellent bactericidal properties at this 4% concentration and above.

Further modifications will also occur to those skilled in this art, and all such are considered to fall within the spirit and scope of the invention as defined inthe appended claims. l

What is claimed is:

1. A process for preparing a non-toxic substance for bactericdal and treating purposes that comprises combining at least one of the heavy and transition metals, including the noble metals, with a carrier non-reactive to the metal, the metals being selected from the group consisting of Ag, 'Au, Pt, Pd, Rh, Cu, Ru, Os, Ir, Tb, Pr, Ce, natural Th, Pa, natural U, Hf, W, V, Re, Zn, Cd, Hg, Ti, Zr, Mo, and Mn, irradiating said metal with radiation having quantum energy at least as high as ultraviolet, maintaining the metal in colloidal particulate form and largely unclustered, and limiting the particle concentration to a range of from about hundredths to about tenths of a percent, by weight.

2. -A non-toxic substance for bactericidal and treating purposes produced by the process of claim 1.

3. A substance as claimed in claim 2 and in which the colloidal particles are in large proportion of the order from substantially 105 to 10-6 cm. in average size.

4. A substance as claimed in claim 2 and in which the particles comprise said metal at least in part dissociated from a chelate thereof.

5. A substance as claimed in claim 4 and in which said substance contains at least one of the family of strychnine alkaloids.

6. A substance as claimed in claim 5 and in which each of strychnine, brucine and reserpine alkaloids is present in said chelate.

7. `A substance as claimed in claim 6 and in which all of said alkaloids are present in content of the order of substantially 0.15 percent by weight.

`8. A substance as claimed in claim 7 and in which the proportions of said strychnine and brucine are approximately equal and yabout twice that of the reserpine alkaloid.

9. A substance as claimed in claim 4 and in which the chelate is of a heavy metal of coordination number 4.

:10. A substance as claimed in claim 2i and in which the particle concentration is of the order of substantially 1.5 103 grams per cubic centimeter.

I11. A substance as claimed in claim 2 and in which the particle concentration is substantially that at which the optimum chemical activity of the metal is attained.

12. A process as claimed in claim 1 and in which said irradiating step is carried out by producing radiation of the order of substantially 1.3 microcuries.

13. A process for preparing a non-toxic substance for bactericidal and curing purposes that comprises combining platinum metal with a carrier non-reactive to the metal, irradiating said metal with radiation having quantum energy at least as high as ultraviolet, maintaining the metal in colloidal particulate form and largely unclustered, and limiting the particle concentration to a range from about 7 8 hundredths to about tenths of a percent, by weight, the 3,172,817 3/ 1965 Leupold etal 424--287 X particles comprising said metal at least in part dissociated 2,329,147 9/ 1943 Troch et al 424-1 X from a chelate thereof.

14. A non-toxic substance for bactericidal and treating BENJAMIN R- PADGETF, Pflmafy Examiner purposes produced by the process of claim 13. 5 U S Cl X R References Cited 204-158 R, 158 HE; 424-132, 141, 145, 146, 262, 288, l UNITED STATES PATENTS 289 290 291 294 2,072,809v 3/1937 Bley 424-1 X 10 

